Oxygen-Binding Sites of Enriched Gold Nanoclusters for Capturing Mitochondrial Reverse Electrons

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Mitochondrial Biology

Background:

• Reverse electron transfer (RET) in mitochondria causes superoxide overproduction.
• This imbalance leads to ischemia-reperfusion injury (IRI) in organs.
• Coenzyme Q (CoQ) redox cycling is central to RET-induced damage.

Purpose of the Study:

• To investigate low-coordinated gold nanoclusters (AuNCs) as electron trappers.
• To explore AuNCs' potential to correct CoQ/CoQH2 imbalance during RET.
• To evaluate AuNCs' efficacy in preventing IRI-induced liver damage.

Main Methods:

• Synthesis of Cs-symmetrical, eight-gold-atom AuNCs with oxygen-binding sites.
• Characterization of AuNCs' electronic structure and oxygen intercalation properties.
• In vitro and in vivo assessment of AuNCs in hepatic IRI models.

Main Results:

• AuNCs exhibited a d-band electron deficiency, facilitating rapid electron capture.
• AuNCs effectively compensated for CoQ/CoQH2 redox cycle imbalances during RET.
• AuNCs treatment prevented inflammation and liver damage in hepatic IRI models.
• Mitochondrial function was restored following AuNCs administration.

Conclusions:

• Low-coordinated AuNCs serve as effective electron-demanding trappers.
• AuNCs mitigate IRI by restoring mitochondrial function and preventing superoxide overproduction.
• This study presents a promising nanocluster-based therapeutic strategy for IRI.